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bioRxiv · 10.1101/2023.11.30.569491

Transcription factor activity profiling reveals the role of REST and LEF1 in the recovery from depression

Yamamoto, H.·Araki, S.·Onodera, R.·Go, Y.·Abe, K.
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Abstract

Psychophysiological disorders chronically impair brain functions, often accompanied by dysregulation of multiple genes, suggesting a multifaceted etiology behind the symptoms. To explore transcription factors (TFs) involved in such transcriptomic changes, we analyzed TF-activity profiles (TFAPs) from the brains of mice experienced chronic stress, and revealed alteration in TF-activity correlating with their pathophysiological phenotypes. We identified REST/NRSF and TCF/LEF associated with depressive phenotypes and discovered that neuropsychiatric drugs sertraline and lithium influence REST- and TCF/LEF-activity, both in vitro and in vivo, thereby affecting gene expression profiles. Pharmacological or genetic manipulation of REST- or TCF/LEF-activity in defeated mice impacts post-stress recovery from depressive phenotypes, with combined treatment further augmenting the outcomes. Our TFAP analysis enhances understanding of molecular mechanisms underpinning chronic diseases, aiding future therapeutic strategy development.

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Yamamoto, H., Araki, S., Onodera, R., Go, Y., Abe, K.. 2023-12-02. Transcription factor activity profiling reveals the role of REST and LEF1 in the recovery from depression. https://doi.org/10.1101/2023.11.30.569491

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